Objective  Primary pulmonary mucoepidermoid carcinoma (PMEC) is a rare malignant lung tumor that accounts for approximately 0.1%–0.2% of all primary pulmonary neoplasms. Due to the non-specific clinical symptoms and epidemiological features, PMEC poses diagnostic challenges.

Methods  Tissue blocks from 23 archived PMECs were collected from The First Affiliated Hospital of Soochow University (November 2012 to December 2023). To establish definitive diagnoses, comprehensive histopathological evaluation, including histomorphological analysis, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and periodic acid-Schiff (PAS) staining were performed.

Results The tumors consisted of varying proportions of mucin-secreting cells (mucous cells), intermediate cells, and epidermoid cells. Immunophenotypically, CK7 was predominantly expressed in the mucous cells, whereas CK5/6, p40, and p63 were expressed in the epidermoid and intermediate cells. The Ki-67 proliferation index ranged from 5% to 60%. All tumors were negative for TTF-1 and Napsin A. Five of the tumors were positive for PD-L1 (clone 22C3), with a tumor percentage score of 3%–20%. All 11 tumors tested for ALK (clone D5F3) were negative. IHC for c-Met was performed on two tumors and both were weakly positive (+). Mastermind-like transcriptional coactivator 2 (MAML2) gene rearrangement was detected in 34.8% (8/23) of the tumors. Mucous cells were PAS positive. Kaplan-Meier survival analysis revealed a significantly poorer prognosis for patients with lymph node metastasis, distant metastasis, advanced TNM stage (Ⅲ+Ⅳ), poor differentiation, or MAML2 gene rearrangement negativity. Univariate analysis identified poor histological differentiation, lymph node metastasis, distant metastasis, and advanced TNM stage as the major prognostic risk factors. Multivariate analysis confirmed poor differentiation and distant metastasis as independent risk factors for adverse outcomes.

Conclusions PMEC is an aggressive tumor with low incidence and non-specific clinical manifestations, leading to frequent misdiagnosis. Clinicians should maintain a high index of suspicion and ensure a thorough differential diagnosis.